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GeneBe

6-132815028-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001016.4(RPS12):c.71C>T(p.Thr24Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RPS12
NM_001016.4 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83
Variant links:
Genes affected
RPS12 (HGNC:10385): (ribosomal protein S12) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S12E family of ribosomal proteins. It is located in the cytoplasm. Increased expression of this gene in colorectal cancers compared to matched normal colonic mucosa has been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS12NM_001016.4 linkuse as main transcriptc.71C>T p.Thr24Ile missense_variant 3/6 ENST00000230050.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS12ENST00000230050.4 linkuse as main transcriptc.71C>T p.Thr24Ile missense_variant 3/61 NM_001016.4 P1
RPS12ENST00000484616.2 linkuse as main transcriptn.153C>T non_coding_transcript_exon_variant 3/62

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251268
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135786
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461556
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152270
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 24, 2022The c.71C>T (p.T24I) alteration is located in exon 3 (coding exon 2) of the RPS12 gene. This alteration results from a C to T substitution at nucleotide position 71, causing the threonine (T) at amino acid position 24 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.067
T
BayesDel_noAF
Pathogenic
0.17
Cadd
Pathogenic
27
Dann
Uncertain
1.0
DEOGEN2
Benign
0.17
T
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.8
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-3.0
D
REVEL
Uncertain
0.34
Sift
Benign
0.19
T
Sift4G
Benign
0.17
T
Polyphen
0.047
B
Vest4
0.90
MVP
0.71
MPC
0.39
ClinPred
0.45
T
GERP RS
5.9
Varity_R
0.55
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142145207; hg19: chr6-133136167; API